This is an R21 exploratory application to obtain preliminary data on a novel approach to treatment of vascular and valvular calcification. Calcification of vascular and valvular structures is a common accompaniment of physiologic aging and is often accelerated in age-related diseases, such as Type II Diabetes. It is now recognized that vascular and valvular calcification are strong predictors of cardiovascular morbidity and mortality. In addition to being a prognostic marker, calcification contributes directly to stiffening of the arterial tree and cardiac valves, causing hydraulic derangements that result in hypertension, ventricular hypertrophy and congestive heart failure. Hence, there is increased interest in understanding the fundamental mechanisms of ectopic calcification, and in identifying effective treatment. In the past, ectopic calcification has been regarded as a passive, degenerative phenomenon, but it is now evident that the deposits exhibit many morphologic and cellular features of skeletal bone formation and remodeling, and that they develop via active metabolic processes. Although calcification may be triggered by specific underlying local pathology, such as inflammation and lipid infiltration, once established, calcium deposition propagates under the influence and regulation of specific osteogenic-cellular, molecular, and hormonal factors. Accordingly, interventions targeting these factors have the potential to retard calcification and preserve normal vascular and valvular function. We propose to investigate an approach based upon recently identified fundamental molecular mechanisms of local soft tissue calcium homeostasis. Animal and cell culture experiments have shown that the PTH/PTHrP receptor, which exists on vascular structures, actively participates in regulating soft tissue calcification, and that activation of this receptor can inhibit calcium deposition. Teriparatide [rhPTH (1-34)], an agonist of this receptor, is the most potent agent in clinical use for increasing bone mineral density in osteoporosis. Our hypothesis is that Teriparatide will retard progression of both ectopic calcification, and the resultant vascular and valvular dysfunction in humans. We propose to test this by conducting longitudinal surveillance in severely osteoporetic patients treated with Teriparatide. This study will provide preliminary data in support of the concept that PTH/PTHrP receptor activation confers a protective effect against soft tissue calcification in humans, and further, may provide a novel approach to therapy. Our specific primary aim (SA#1) is to compare the effect of Teriparatide on one-year progression of coronary artery calcification in Teriparatide-treated, versus matched non-treated control subjects with 64- element computed tomography (MDCT). Secondary aims are to assess one-year progression of: 1) Aortic valve calcification by MDCT (SA#2a); 2) Aortic valve area by Doppler-Echo continuity (SA#2B); 3) aortic compliance measured by pulse wave velocity and pulse augmentation index (SA#2c). [unreadable] [unreadable] [unreadable]